#VisualAbstract: Methylprednisolone in severe COVID-19 pneumonia associated with clinical benefit in those with high baseline serum ferritin

1. Methylprednisolone therapy in nonintubated patients with COVID-19 receiving high-flow oxygen therapy was associated with clinical benefit solely in patients with baseline serum ferritin levels in the upper tertile of values.
2. In contrast, for patients with ferritin in the lower and middle tertiles, no association with benefit was observed.

Evidence Rating Level: 2 (Good)

Study Rundown: To date, therapeutic options for severe COVID-19 infection are limited, where steroid therapy have shown benefits in targeting the inflammatory overresponse caused by SARSCoV-2 that may lead to acute respiratory distress and potential death but may also be harmful in patients with milder forms of the disease. Serum ferritin, an acute phase reactant of inflammation, may play a role in evaluating the risks and benefits of steroid therapy in various severities of COVID-19 disease. This retrospective cohort study evaluated whether admission serum ferritin could be a possible surrogate of a phenotype associated with clinical response to methylprednisolone in nonintubated adults with severe COVID-19 pneumonia receiving high-flow oxygen therapy. The main endpoint of the analysis was mortality, where secondary endpoint was a composite of death or mechanical ventilation use at 28 days. Among 380 patients with severe COVID-19 pneumonia, methylprednisolone was associated with lower mortality and reduced rates of death or mechanical ventilation only in patients with serum ferritin levels in the upper tertile of values (1,322-13,418 ng/mL), with no beneficial association among individuals with lower admission ferritin values. These results suggested that methylprednisolone therapy in nonintubated patients with COVID-19 receiving high-flow oxygen therapy was associated with clinical benefit solely in patients with baseline serum ferritin levels in the upper tertile of values. In contrast, for patients with ferritin in the lower and middle tertiles, no association with benefit was observed. A limitation of this study was that serum ferritin levels were only available in 85% of eligible patients during the enrollment period, introducing possible bias among tertiles with influence on methylprednisolone efficacy.

Click to read the study in JAMA Network Open

Relevant Reading: Methylprednisolone as adjunctive therapy for patients hospitalized with coronavirus disease 2019 (COVID-19; Metcovid): a randomized, double-blind, phase IIb, placebo-controlled trial

In-Depth [retrospective cohort]: This retrospective cohort study included 380 patients with severe COVID-19 (median [IQR] age, 60 years [49-72] years; 130 [34.2%] women; 310 White [81.6%]; 47 Black [12.4%]; 23 Asian [6.1%]) admitted to an academic tertiary center in Stony Brook, New York from March to April 2020, with a follow-up of 28 days and data analysis completed in July 2021. All patients received high-flow oxygen therapy (FiO2, ≥50%) and 142 patients (37.4%) received systemic methylprednisolone (median [IQR] daily dose, 160 [120-240]mg) as the exposure. The outcomes of treatment with methylprednisolone were estimated using inverse probability of treatment weights, based on a propensity score comprised of clinical and laboratory variables. Overall, ferritin levels were similar in patients who received methylprednisolone compared to those who did not (median [IQR], 992 [509-1610] ng/mL vs 893 [474-1467] ng/mL; P = .32). Weighted analyses via tertiles of ferritin values (lower: 29-619 ng/mL; middle: 623-1316 ng/mL; upper: 1,322-13,418 ng/mL) showed methylprednisolone was associated with lower mortality in patients from the upper ferritin tertile (HR, 0.16; 95%CI, 0.06-0.45) and higher mortality in those from the middle (HR, 2.46; 95%CI, 1.15-5.28) and lower (HR, 2.43; 95%CI, 1.13-5.22; P < .001) tertiles. Analysis of secondary outcomes focused on a composite endpoint of death or mechanical ventilation use at 28 days were lower in patients on methylprednisolone from the upper ferritin tertile (HR, 0.45; 95%CI, 0.25-0.80) but not in those from the middle (HR, 0.83; 95%CI, 0.50-1.39) or lower (HR, 0.89; 95%CI, 0.51-1.55; P = .11) tertiles.

Image: PD

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